Protein kinase phosphorylation sites

Jiang, D., and Sibley, D. R. (1999) Regulation of D(l) dopamine receptors with mutations of protein kinase phosphorylation sites attenuation of the rate of agonist-induced desensitization. Mol. Pharmacol. 56, 675-683. 

Pearson, R.B. and Kemp, B.E. Protein kinase phosphorylation site sequences and consensus specificity motifs tabulations (1991) Methods in Enzymol. 200, 62-81... 

Mahrenholz, A.M., Hefta, S.A. and Mansour, T.E. (1991) Phosphofructokinase from Fasciola hepatica sequence of the cAMP-dependent protein kinase phosphorylation site. Archives in Biochemistry and Biophysics 288, 463 167. 

Butt, E., Abel, K., Krieger, M., Palm, D., Hoppe, V., Hoppe, J., Walter, U. (1994). cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets. J. Biol. Chem. 

B.J. Wam-Cramer, P.D. Lampe, W.E, Kurata, M.Y. Kanemitsu, L.W. Loo, W. Eckhart, A.F. Lau, Characterization of the mitogen-activated protein kinase phosphorylation sites on the connexin-43 gap junction protein,./ Biol Chem 271,3779-3786 (1996). 

Ikebe M, Hartshorne DJ, Elzinga M (1987a) Phosphorylation of the 20,000-dalton light chain of smooth muscle myosin by the calcium-activated, phospholipid-dependent protein kinase. Phosphorylation sites and effects of phosphorylation. J Biol Chem 262 9569-9573... 

Li, L., Zhou, J., James, G., Heller-Harrison, R, Czech, M.P. and Olson, E.N. (1992) FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains. Cell 71, 1182-1194. 

FIGURE 1 2-2 Schematic diagram of the phosphorylation sites on each of the four 60kDa subunits of tyrosine hydroxylase (TOHase). Serine residues at the N-terminus of each of the four subunits of TOHase can be phosphorylated by at least five protein kinases. (J), Calcium/calmodulin-dependent protein kinase II (CaM KII) phosphorylates serine residue 19 and to a lesser extent serine 40. (2), cAMP-dependent protein kinase (PKA) phosphorylates serine residue 40. (3), Calcium/phosphatidylserine-activated protein kinase (PKC) phosphorylates serine 40. (4), Extracellular receptor-activated protein kinase (ERK) phosphorylates serine 31. (5), A cdc-like protein kinase phosphorylates serine 8. Phosphorylation on either serine 19 or 40 increases the activity of TOHase. Serine 19 phosphorylation requires the presence of an activator protein , also known as 14-3-3 protein, for the expression of increased activity. Phosphorylation of serines 8 and 31 has little effect on catalytic activity. The model shown includes the activation of ERK by an ERK kinase. The ERK kinase is activated by phosphorylation by PKC. (With permission from reference [72].)... 

Fredericks, Z. L., Pitcher, J. A., and Lefkowitz, R. J. (1996) Identification of the G protein-coupled receptor kinase phosphorylation sites in the human beta2-adrenergic receptor. J. Biol. Chem. 271, 13796-13803. 

Seibold, A., January, B. G., Friedman, L, Hipkin, R. W., and Clark, R. B. (1998) Desensitization of beta2-adrenergic receptors with mntations of the proposed G protein-con-pled receptor kinase phosphorylation sites. J. Biol. Chem. 273, 7637-7642. 

In its active form CheA undergoes autophosphorylation, that is, the phosphorylation of a histidine imidazole group in one of its subunits by the protein kinase active site of an adjacent subunit. The phospho group is then transferred from phospho-CheA to another protein, CheY. Phospho-CheY interacts with the flagellar motor proteins (Chapter 19) periodically causing a reversal of direction of the bacterial flagella. As a result the bacteria tumble and then usually move... 

He Q, Dent EW, Meiri KF (1997) Modulation of actin filament behavior by GAP-43 (neuromod-ulin) is dependent on the phosphorylation status of serine 41, the protein kinase C site. J Neu-rosci 17 3515-24... 

As mentioned above, cAMP-dependent protein kinase phosphorylates and inactivates liver and muscle glycogen synthase [85,86]. Phosphorylation occurs at several serine residues in the muscle enzyme designated la, lb, 2, 3 and 4 [87-90] and it is probable that the phosphorylation pattern is similar in the liver enzyme [91,92]. Phosphorylation of site 1 of the muscle enzyme occurs more rapidly than the other sites [87], and sites 3 and 4 have only recently been recognized as phosphorylation sites [89]. All the sites are surrounded by amino acid sequences characteristic for cAMP-dependent protein kinase [90,93,94]. 

When working with purified enzymes, it can be useful to perform a close examination of their phosphorylation states and molecular masses. Mass spectrometry is often useful for this purpose. Post-translational modifications or sequence truncations can potentially alter the compound binding sites available and can also change the structure of potential inhibitory sites. For example, with protein kinases, phosphorylations distal from the ATP binding site can inactivate the kinase whereas phosphorylations near the ATP binding site can activate the catalytic activity. Often, practice does not permit control of such situations because the purified systems are often mixtures and cannot be controlled in the commonly used recombinant expression technologies. 

Software predictions suggest a number of potential phosphorylation sites in the coronin 7 protein. The highest E value predictions are for potential MAP kinase phosphorylation sites at serine residue 442 and threonines 497 and 733, cdc2 sites at S-450 and S-775, cdk5 at S-437, PKC sites at S-7, S-465 and T-654 and Src sites at tyrosine residues 288 and 758. Not surprisingly, many serine and threonine phosphorylation predictions concentrate in the low complexity PST-enriched region. Although it remains to be elucidated which of the predicted sites are relevant in vivo, at least some of them have been experimentally demonstrated to be phosphorylated in vitro (see below). 

CatteraU There is a protein kinase C site that is phosphorylated and has subtle effects. We have looked for proteins that interact with the 3—4 linker, but we haven t found any in a range of protein—protein interaction assays. We have considered the idea that something inside the cell binds the gate in an open conformation and keeps it open. This may be true, but we haven t been able to demonstrate it. 

West JW, Numann R, Murphy BJ, Scheuer T, CatteraU WA 1992 Phosphorylation of a conserved protein kinase C site is required for modulation of Na currents in transfected Chinese hamster ovary cells. Biophys J 62 31—33... 

The transcription factors regulated by the JNK/SAPK and p38 proteins include the Elkl, ATF2, and c-Jun proteins. As expressed by their name, the c-Jun terminal protein kinases phosphorylate the c-Jun protein at residues Ser63 and Ser73. These phosphorylation sites are located within the transactivation domain of c-Jun, and their phosphorylation correlates with enhanced trans-activating activity. 

As seen in T able 14, there are two phosphorylation sites at the N-terminal region of the rabbit skeletal muscle glycogen synthase. The remaining seven are situated at the C-terminal region. The cAMP-dependent protein kinase preferentially phosphorylates three sites, la, lb, and 2. The cAMP-dependent kinase can also phosphoryiate sites 3a and 4 but at a much slower rate and thus is not considered to be as important as glycogen synthase kinase 3 for those sites. There are overlapping specificities among the different protein kinases for site 2 as phosphorylase kinase, calmodulin-dependent protein kinase and protein kinase C also can phosphoryiate this site. ... 

A critical site is Ser-505, the site phosphorylated by mitogen-activated protein kinase. Phosphorylation at this site increases the activity of the enzyme both in vitro and in vivo. However, other phosphorylation sites may also be involved in particular, Ser-727 may also have an important role in some cell systems [23]. The Ser-505 is located in a flexible loop that connects the C2 and catalytic domains (Fig. 9). It is possible that phosphorylation of this residue produces the optimum orientation of the two domains with respect to the membrane interface (S. Das, 2003). Overall, it is probable that the role of phosphorylation in translocation, membrane binding, and enzyme activation depends on the cell type and the nature of the stimulus [23]. 

---